Fetal neural progenitor, or stem cells are multipotent cells that are useful for various therapeutic applications involving their implantation into humans but significant moral, ethical, and technological issues make the use of these cells undesirable. Such problems include immunological rejection and potential contamination.
It has been reported that the entire ventricular neroaxis, including the spinal cords of adult mammals, contain stem cells (Morshead and Van der Kooy, Journal of Neuroscience, 12:249-256, 1992; Reynolds and Weiss, Science, 255:1707-1710, 1992; Lois and Alvarex-Buyalla, Science, 264:1145-1148, 1994; Morshead et al., Neuron, 13:1071-1082, 1994; Weiss et al., Trends in Neuroscience, 19:387-393, 1996a, Journal of Neuroscience, 16:7599-7609, 1996 b). These stem cells may proliferate and expand in some circumstances and are affected by growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitor factor (LIF), and others; the stem cells may then differentiate into other cell types, including neurons, astrocytes, and oligodendrocytes (Reynolds and Weiss, 1992; Morshead et al., 1994; Weiss et al., 1996b). Recent data demonstrate that adult subventricular zone astrocytes or astrocyte progenitors can develop into stem cells in vivo (Doetsch, 1999).
An approach to isolating stem cells and differentiating them into other cell types has been reported. First, nervous system stem cells are isolated from human embryonic or adult brain; the technical and economic challenges of this technique make it difficult to use this process for producing cells for human implantation (Svendsen et al., Experimental Neurology, 137:376-388, 1996; Chalmers-Redman et al., Neuroscience, 76:1121-1128, 1997; Carpenter et al., Experimental Neurology, 158:265-278, 1999; Fricker et al., Journal of Neuroscience, 19:5990-6005, 1999; Kudekov et al., Experimental Neurology, 156:333-334, 1999; Vescovi et al., Experimental Neurology, 156, 71-83, 1999). These cells are transplanted into adult rodent brain, where they differentiate into neurons, glial cells, and associated cells, with no tumor formation (Vescovi et al., 1999).
A substantial body of literature describes therapies based on introducing cells into patients. These therapies include treatments of Alzheimer's, Parkinson's disease, and in vivo drug delivery. Examples of such therapies are described in “Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain” by F. H. Gage et al., Proceedings of the National Academy of Science U.S.A. 92:11879-83 (1995); “Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain” by R. A Fricker et al., Journal of Neuroscience, 19:5990-6005 (1999); and “Self-repair in the brain” by A. Bjorklund and 0. Lindvall, Nature 405:892-3, 895 (2000), which are hereby incorporated by reference.